Zhang Liqun, Ghosh Santosh K, Basavarajappa Shrikanth C, Muller-Greven Jeannine, Penfield Jackson, Brewer Ann, Ramakrishnan Parameswaran, Buck Matthias, Weinberg Aaron
Chemical Engineering, Tennessee Technological University, Cookeville, TN 38505.
contributed equally.
bioRxiv. 2021 Jan 7:2021.01.07.425621. doi: 10.1101/2021.01.07.425621.
New approaches to complement vaccination are needed to combat the spread of SARS-CoV-2 and stop COVID-19 related deaths and long-term medical complications. Human beta defensin 2 (hBD-2) is a naturally occurring epithelial cell derived host defense peptide that has antiviral properties. Our comprehensive studies demonstrate that hBD-2 binds the site on the CoV-2-RBD that docks with the ACE2 receptor. Biophysical and biochemical assays confirm that hBD-2 indeed binds to the CoV-2-receptor binding domain (RBD) (K ~ 300 nM), preventing it from binding to ACE2 expressing cells. Importantly, hBD-2 shows specificity by blocking CoV-2/spike pseudoviral infection, but not VSV-G mediated infection, of ACE2 expressing human cells with an IC of 2.4± 0.1 μM. These promising findings offer opportunities to develop hBD-2 and/or its derivatives and mimetics to safely and effectively use as novel agents to prevent SARS-CoV-2 infection.
需要新的补体疫苗接种方法来对抗SARS-CoV-2的传播，并阻止与COVID-19相关的死亡和长期医学并发症。人β-防御素2（hBD-2）是一种天然存在的上皮细胞衍生的宿主防御肽，具有抗病毒特性。我们的综合研究表明，hBD-2与冠状病毒2受体结合域（CoV-2-RBD）上与ACE2受体对接的位点结合。生物物理和生化分析证实，hBD-2确实与CoV-2受体结合域（RBD）结合（K~300 nM），阻止其与表达ACE2的细胞结合。重要的是，hBD-2通过阻断表达ACE2的人细胞的CoV-2/刺突假病毒感染，而不是VSV-G介导的感染，显示出特异性，其IC为2.4±0.1μM。这些有前景的发现为开发hBD-2和/或其衍生物及模拟物提供了机会，以安全有效地用作预防SARS-CoV-2感染的新型药物。
